SARI及PI3K/AKT通路分子在AML患者骨髓中的表达及其临床意义

Expression and clinical significance of SARI and PI3K/AKT pathway molecules in bone marrow of AML patients

目的:探讨SARI及PI3K/AKT通路分子在急性髓系白血病(acute myeloid leukemia, AML)患者骨髓中的表达情况及其临床意义。方法:收集100例AML患者的骨髓标本,并以30例造血干细胞移植健康供者作为正常对照。分别采用qPCR和Western blot检测SARI及PI3K/AKT通路分子的mRNA及蛋白表达。结果:AML患者骨髓中SARI mRNA的表达低于正常对照(P<0.05),且初诊和复发组中SARI mRNA和蛋白表达量均低于缓解组(P<0.05)。ROC曲线分析显示当SARI mRNA的截断值为0.191时,诊断AML的AUC为0.705,灵敏度为70.0%,特异度为66.2%;SARI mRNA高表达组AML初诊患者的缓解率高于未缓解率(P<0.05),配对t检验分析显示同一AML患者其初诊阶段SARI mRNA表达明显低于缓解阶段(P<0.05);Kaplan-Meier生存分析显示SARI mRNA高表达组AML患者总生存时间长于低表达组(P<0.05)。初诊和复发组中PI3K、AKT、mTOR、4EBP1 mRNA表达均高于缓解组(P<0.05);除p-AKT外,初诊和复发组中上述分子及对应的磷酸化分子p-PI3K、p-mTOR、p-4EBP1蛋白表达均明显高于缓解组(P<0.05),且均与SARI蛋白表达呈负相关(P<0.05)。结论:SARI在AML骨髓中异常低表达,与患者疗效、预后密切相关,其机制涉及PI3K/AKT通路的激活。SARI可作为AML诊断、疗效与预后评估的新指标。

Objective:To investigate the expression and clinical significance of SARI and PI3K/AKT pathway molecules in acute myeloid leukemia(AML)patients.Methods:100 AML patients'bone marrow were collected and 30 healthy hematopoietic stem cell donors'as controls.The mRNA and protein expression of SARI and PI3K/AKT pathway molecules were detected by qPCR and Western blot,respectively.Results:The expression of SARI mRNA in AML patient was lower than control(P<0.05),and the expression of SARI mRNA and protein in newly diagnosed and relapsed group was both lower than remission group(P<0.05).ROC curve analysis showed that when the cutoff value of SARI was 0.191,the AUC for AML was 0.705,the sensitivity was 70.0% and the specificity was 66.2%.The remission rate of AML patients with SARI mRNA high-expression was higher than non-remission rate( P <0.05),paired t -test analysis showed that the expression of SARI mRNA in the newly diagnosed stage of the same AML patients was lower than remission stage( P <0.05).The Kaplan-Meier survival analysis showed that the overall survival time of AML patients with SARI mRNA high-expression was longer than low-expression( P <0.05).The mRNA expressions of PI3K,AKT,mTOR and 4EBP1 in the newly diagnosed and relapse group were both higher than remission group( P <0.05).Except for p-AKT,the protein expression of the above-mentioned molecules and their corresponding phosphorylated molecules p-PI3K,p-mTOR,p-4EBP1 in the newly diagnosed and relapsed group was both higher than remission group( P <0.05),and was negatively correlated with the expression of SARI protein( P <0.05). Conclusion: The abnormally low expression of SARI is closely related to the therapeutic effect and prognosis of the AML patients,and the mechanism involves the activation of PI3K/AKT pathway.SARI can serve as an new marker for AML diagnosis,therapeutic effect and prognosis of AML.